Avena sativa, or common oats, is an annual grain which is widely cultivated for its edible grain, sometimes called groats. Beneficial properties have long been attributed to oats, as evidenced by such common expressions as "feeling your oats." Persons who ascribe to "natural medicine" or "herbal science" have included oats in their armamatum of purportedly therapeutic preparations. Indeed, over the years scattered reports of pharmacological activity attributable to some component in oats have appeared in the traditional scientific literature, most recently with respect to the cholesterol-lowering properties of oat bran.
There have been reports in the popular literature of the use of alcoholic extracts of Avena sativa as treatments for both opiate addiction and cigarette smoking. However, the scientific literature has not documented any anti-addictive activity of any of the chemically defined compounds in Avena sativa.
Handler, in The Doctors' Vitamin and Mineral Encyclopedia, Simon and Schuster, New York, 1990, 318-319, notes that there have been claims that oats have anti-depressant and aphrodisiac properties, and there is some evidence that oats can aid people in overcoming drug habits. A decoction of common oats has been successfully used in Ayurvedic medicine to treat opium addiction. It was noted along the way that several opium addicts, in addition to curbing opium withdrawal, also lost interest in smoking cigarettes after using an alcoholic extract of the oat plant. Anand, in Nature, 233: 496, 1971, described an experiment in which chronic cigarette smokers were given an extract of fresh Avena sativa. This study was placebo controlled, and found that, after one month, there was a significant decrease in the number of cigarettes smoked by those using oat extract when compared to those using a placebo. A diminished craving was definitely noted, and the effect continued two months after the oat extract treatments had ceased. A subsequent study on mice suggested that the oat extract contains substance that is antagonistic to morphine. The claimed anti-depressant and aphrodisiac properties of oats have never been convincingly demonstrated.
According to Lust, in The Herb Book, Bantam Books, New York, 1974, 286-287, oats are used primarily for their nutritional value. They are particularly beneficial in special diets for convalescents or those with certain illnesses, including gastro-enteritis and dyspepsia. Oat extract and tincture are useful as nerve and uterine tonics. A tea made from oat straw has been recommended for chest problems.
Saeed et al., in Biochemical Society Transactions, 9(5):444 (1981), reported on an evaluation of extracts of oats in inhibiting prostaglandin biosynthesis. Extracts of Avena sativa were found to possess strong inhibitory activity of prostaglandin biosynthesis, which may explain the anti-inflammatory effects of oats on certain inflammatory conditions of the skin, including itch, sunburn, and like conditions.
Tschesche et al., in Tetrahedron, 29: 629-633, 1973, report the extraction of an antibiotic active glycoside, avenacine B, from the roots of Avena sativa. This glycoside was isolated in addition to the main glycoside, avenacine A. The aglycone B substitutes a methyl group for the hydroxymethyl group of the aglycone A.
Erickson, in Photochem. Photobiol. 49(4): 479-483, 1989, disclose the visualization of a highly purified photochrome from Avena sativa by electron microscopy after negative staining with uranyl acetate and after rotary shadowing with platinum. The particle shape was variable in both types of specimens, but tripartite structures resembling a "Y" were consistently observed. The tripartite substructure is composed of three globular domains, each having a diameter of 7 to 8 nm and equally spaced in an equilateral triangle. The dimensions of the tripartite particle measured 15 nm between the centers of any two of the three particles. When the phytochrome was digested with trypsin to release the amino-terminal globular domain from the polypeptide, the tripartite structure was lost. It was proposed that the outer particles of the tripartite structure are the amino-terminal domains of the phytochrome dimer, and the central particle comprises the carboxyl domains of the two subunits.
The tetrahydropyranone structure is a major feature of a series of aromatic compounds obtained from piper methysticin Forst, the Polynesian kava--kava plant, also known as intoxicating pepper. A number of aromatic pyrones have been identified in kava--kava extracts; all of these compounds are unsaturated across the 3,4-positions and contain a methoxy group in the 4-position: ##STR2##
The compounds identified in the kava kava include kawain, dihydrokawain, methysticin, dihydromethysticin, yangonin and desmethoxyyangonin. These compounds are well known in the popular literature, and have been studied for a number of pharmacological activities.
Kava kava has a long history of use in the Polynesian islands, particularly Fiji. Traditionally, the upper rhizome is made into a tea. The tea was considered to act as a mild stimulant and tonic. Another method of treating the plant involved first chewing on the root, spitting it into a bowl, and then soaking it in coconut milk. This preparation reportedly possesses narcotic-like properties.
The primary effects of kava kava extract are initially, and at low dose, euphoric. Larger doses produce extreme relaxation, lethargy of the lower limbs, and finally, sleep. Frequently, larger doses of kava kava may produce visual and auditory hallucinations. Chewing the kava kava root produces a numbing of the mouth.
A number of studies have appeared in the scientific literature, and are referenced in the Merck Index.
Kretzschmar et al., in Arch. Int. Pharmacodyn 177: 261-277, 1969, report an investigation into the anticonvulsant activities of the kava compounds. All six kava-pyrones were used to antagonize convulsions in mice caused by maximal electroshock and phenyltetrazol. The results were compared to standard anti-convulsants, including dilantin and phenobarbital. All six kava compounds were found to be active as anti-convulsants. However, the effects were more similar to the effects of local anesthetics such as procaine than to the traditional anti-convulsants. The anticonvulsant effect was antagonized by pretreatment with reserpine. No structure-activity relationships were apparent for intravenous dosage. The effective dose was between 5 and 10 mg/kg. The lethal dose was between four and ten times higher for i.v. administration, and about 1 gram/kg for oral administration. These results suggest a neurotransmitter mediated mechanism due to the antagonism by reserpine, and possibly an effect on membrane channels to account for the procaine-like effects.
In Arch. Int. Pharmacodym 180: 475-491, 1969, Kretzschmar et al. report studies of the spasmolytic activities of the kava-pyrones using the guinea pig isolated ileum preparation. All six of the kava compounds were found to have spasmolytic activity. Histamine, 5-HT, acetylcholine and nicotine were used to induce muscle contractions, and the ability of the kava pyrones to antagonize this activity was tested. The kava-pyrones were found to antagonize the effects of all of the stimulants. Thus, the mechanism of the kava-pyrones was not due to a specific receptor-mediated mechanism at the transmitter level but were considered to be direct musculotropic actions similar to that of papaverine. The kava-pyrones were most potent against contractions due to nicotine and 5-HT, and less active against acetylcholine and histamine. The authors again attempted to compare the results with those obtained by local anesthetics, and found the highest correlation with benzocain and cocaine and less correlation with procaine. There was a clear relationship between structure and activity for the kava pyrones: compounds which are completely saturated in the pyrone ring, i.e., the tetrahydropyrones, were more effective than compounds that were saturated in the 5,6-position, the dihydropyrones. Substitution on the benzene ring of these compounds was found to alter their activity. No compounds lacking the 4-methoxy group on the pyrone ring were tested.
Gamma and delta lactones are known to be flavor and fragrance compounds. Methods of producing such lactones are disclosed, for example, in Page et al., PCT application WO89/12104. Japanese patent 63/275514 discloses lactone compounds for use in hair tonics for inhibiting the activity of testosterone-5-reductases.
Voltage-gated potassium channels make up a large molecular family of integral membrane proteins that are fundamentally involved in the generation of bioelectric signals such as nerve impulses. These proteins span the cell membrane, forming potassium-selective pores that are rapidly switched open or closed by changes in membrane voltage. Several chemical entities have been discovered to be potent and specific openers of vascular potassium channels. These include cromakalim and its derivatives and RP 52891. This mechanism is also shared, at least partially, by drugs such as minoxidil, diazoxide, pinacidil and nicorandil. The opening of plasmalemmal K.sup.+ channels produces loss of cytosolic K.sup.+. This effect results in cellular hyperpolarization and functional vasorelaxation. In normotensive or hypertensive rats, K.sup.+ channel activators decrease aortic blood pressure (by producing a directly mediated fall in systemic vascular resistance) and reflexly increase heart rate. K.sup.+ channel openers produce selective coronary vasodilatation and afford functional and biochemical protection to the ischemic myocardium.